Preliminary results have demonstrated both functional and morphological abnormalities in parotid glands of streptozotocin-diabetic rats compared with nondiabetic controls. Of particular, interest, the rate of secretion from the parotid gland in diabetic animals evoked by parasympathetic nerve stimulation were reduced, and numerous terminal axons evidenced signs of an initial axonopathy. The integrity of salivary gland function is dependent of an intact autonomic innervation, and these studies may provide valuable insights into the etiology, pathophysiology and treatment of diabetic autonomic neuropathy. However, differences observed between diabetic and control rats during parasympathetic stimulation may also result from altered cells responses to stimulation, or from other systemic effects of diabetes. Therefore, we propose to investigate the effects of diabetes on 1) the response of parotid glands in vivo and in vitro to adrenergic, cholinergic and peptidergic agonists, 2) the number, affinity and functional coupling of adrenergic, cholinergic and peptidergic receptors, and 3) the morphology and neurobiochemistry of autonomic nerves supplying the parotid glands. The goal of this and future research is to elucidate the pathogenesis of parotid gland dysfunction in diabetes, thereby determining the relative role of neural dysfunction and altered end-organ metabolism in this process.